Normal skin healing following a wound or injury is a complex and dynamic process involving the restoration of cellular structures and tissue layers following injury to the skin and other soft tissues. The healing process is generally thought to occur in three phases.
Firstly there is a clotting phase in which blood-thickening proteins and blood platelets seal a wound to prevent blood loss. Then there is an inflammatory phase in which white blood cells are sent to fight infection. Finally there is a repair phase in which tissue cells restore integrity to damaged areas.
All wound healing usually results in scarring to some extent which is caused by the incomplete restoration of initial skin structure and the disruption of the normal alignment of collagen fibers.
In addition, there are specific illnesses and diseases which can result in chronic skin wound and injuries, such as diabetes ulcers and ulcerous wounds. Also other conditions, such as paralysis and old age, can result in serious skin injuries as a result of pressure inflicted wounds such as eschars.
The muscular cardiac tissue is made of cardiomyocytes. These specialized forms of muscle cells are not capable of regeneration following injury in the adult. Common injuries to the heart muscle occur in ischemic heart attacks during which blood flow to the heart is restricted and the cardiac muscle is damaged through hypoxia. Patients suffering from heart infarct require both the restoration of blood supply to the heart and the regeneration of the damaged heart muscle.
The central nervous system composed of neurons and other nerve cells is generally incapable of regeneration in the adult and the peripheral nervous system is only capable of limited regeneration. Illnesses that commonly result in central nervous system damage are multiple sclerosis and amyotrophic lateral sclerosis. Incidents that commonly result in central nervous system damage are spinal cord damage and cerebral vascular accidents.
Urinary incontinence can result from damage to the sphincters of the urethra.
Various conditions can result in liver damage including viral hepatitis, cirrhosis, steatohepatitis and liver cancer.
Similarly damage and degeneration of the pancreas can result in diabetes.
Arthritis is a form of degradation and damage to the joints between bones.
There is thus a need to produce therapeutic strategies for improving these conditions, whether they are the result of a pathology or the natural imperfection of skin-healing, or incapacity for heart tissue or nervous tissue or cartilage or joints or liver or urethral sphincters to regenerate or diabetes caused by the degeneration of pancreas. Additionally there is a need for therapeutic strategies for promoting angiogenesis generally and specifically for treating erectile dysfunction.
Fathke et al (Stem Cells 2004; 22:812-822) have shown that following an injection of bone marrow stem cells in mice, these stem cells contributed to the population of regenerated skin cells in normal conditions. It was further shown that bone marrow stem cells contributed to dermal fibroblasts regeneration and transcribed Collagen type I and III, Collagen type III being specific to these stem cells derived from bone marrow. The stem cells were transplanted either systemically by injection into the bloodstream of a different animal to the donor or directly in the bone marrow of the recipient. No improvement on the quality or speed of the healing was shown.
In the publication by Bang O. Y et al, Ann Neurology 2005, June; 57(6): 874-82, there is described the transplantation of autologous mesenchymal stem cells being bone marrow mononuclear cells for the treatment of ischemic strokes. These cells were separated by the Ficoll density separation of bone marrow and were cultured and expanded before re-implantation. In addition they did not express CD34 or CD45. No functional improvement was observed following treatment.
In the publication by Mazzini et al, (The Lancet 2004; 354: 1936-1937), there is described the transplantation in the spinal cord of autologous mesenchymal stem cells for the treatment of amyotrophic lateral sclerosis. The results described only showed a slowing down of the decline of the forced vital capacity of some patients but no improvement.